Method of Providing Fast Relief to a User of a Nicotine Chewing Gum

ABSTRACT

The invention relates to a method of relieving nicotine craving comprising the steps of providing at least one chewing gum comprising tobacco alkaloid to a user, providing relief of nicotine craving to said user by transferring of tobacco alkaloid from the chewing gum to the human body of said user by chewing of said chewing gum, said chewing of said chewing gum comprising a chewing process involving a transfer of tobacco alkaloid from said chewing gum above a threshold transfer rate in the period of about ½ minute to about 2½ minutes from initiation of said chewing process.

BACKGROUND OF THE INVENTION Craving or Addiction:

Medical and scientific communities in the US agree that nicotine isaddictive. Nicotine meets both the psychological and physiologicalmeasures of addiction:

Psychological—people who are addicted to something will use itcompulsively, without regard for its negative effects on their health orlife. A good example would be someone who continues to smoke, even asthey use an oxygen tank to breathe because of the damage smoking hasdone to their lungs.

Physiological—neuroscientists call anything that turns on the rewardpathway in the brain addictive. Because stimulating this neuralcircuitry makes you so good, you will continue to do it again and againto get those feelings back.

When smokers abruptly stop smoking—the body cannot function the same wayin the absence of the drug as it did before, the physiological effectsfor nicotine remain, at least in the short term. They will experience:Irritability, anxiety, depression and craving for nicotine.

Over a period these symptoms and physiological changes subside. It is inthis period alternative methods of nicotine delivery is essential inorder to succeed quitting smoking.

Nicotine:

Nicotine normally makes up about 5% of a tobacco plant, by weight.Cigarettes contain 8-20 mg of nicotine depending on the brand, but onlyapproximately 1 mg is actually absorbed by your body when you smoke acigarette.

Nicotine's effects are short-lived, lasting only 40 minutes to a coupleof hours. This leads people to smoke tobacco periodically throughout theday to dose themselves with nicotine. Within 10-15 seconds of inhaling,most smokers are in the throes of nicotine's effects.

Different approaches may be made in order to counteract craving relatedto absence of nicotine in the blood.

Many pharmacotherapies have been developed or explored for aidingsmokers to cease smoking. The predominant one is nicotine replacementtherapies. Nicotine replacement therapies involve the administration ofnicotine through suitable delivery systems. Nicotine replacementproducts available on the market include nicotine transdermal patches,inhalators, nicotine nasal spray or nicotine chewing gum. These types ofproducts, like cigarettes, deliver nicotine to the blood via diffusionof nicotine through the skin or the mucous membrane.

Nicotine transdermal patches release nicotine into the bloodstreamthrough the skin. A patch is applied each day to a different area ofdry, clean, non-hairy skin and left as long as recommended on theproduct labelling—typically the non-sleeping hours of a day. Using theproduct generates a constant low concentration of nicotine to the bloodover the period applied.

Nicotine nasal spray is inhaled into the person's nose from a pumpbottle and absorbed through the nasal lining into the bloodstream. Thisform of nicotine delivery system generates a fast increase of nicotineconcentration in the blood—almost as fast as the cigarette.

Nicotine inhalator enters the user's mouth through a mouthpiece attachedto a plastic cartridge. Although the product is called an “inhaler”, itdoes not deliver nicotine to the lungs the way a cigarette does. Almostall of the nicotine travels only as far as the mouth and throat, whereit is absorbed through the mucous membrane.

Nicotine chewing gum releases nicotine into the bloodstream through thelining of the mouth, i.e. the mucous membrane. Unlike gum chewed forpleasure, nicotine gum requires a measured routine—it is chewed slowlyuntil a slight tingling occurs or a peppery taste comes out, then it isplaced between the check and gum until the taste or tingling is almostgone. The cycle is typically repeated for about 30 minutes per gum.Products available slowly build up the nicotine blood concentration overthe first 10-15 minutes of chewing.

The present invention relates to counteracting of craving by means ofnicotine holding chewing gum.

Counteracting of craving by means of nicotine holding chewing gum assuch is well-known within the art.

Basically two different paths have been followed in the prior art, aloneor in combination.

The original approach was to incorporate nicotine in chewing gum andthen match the release of chewing gum with the overall total desiredrelease of nicotine over the entire chewing period. Typically, such anapproach involves considerations with respect to the release of nicotineover a day compared to one or several different smoking patterns.

A further attempt to improve the counteracting of craving by means ofchewing gum is to incorporate nicotine in e.g. the coat of a coatedchewing gum. Such an approach may be referred to as biphasic within theart, i.e. the approach of providing an initial significant dose ofnicotine immediately after chewing of a chewing gum has been initiatedand then subsequently, providing a second long term dose subsequently.Such subsequent dose is also referred to as maintenance dose may e.g.last from about 10 minutes to 30 minutes of the chewing process.

A problem related to the prior art is however that some users of thechewing gum may dislike especially the initial dose and that thesubsequent dose typically mismatches the expectations of the user withrespect to relieving of nicotine related craving.

It is the object of the invention to obtain a chewing gum, which may beapplied for an effective and user-acceptable counteracting of cravingnot only after use but also during use.

SUMMARY

The invention relates to a method of relieving nicotine cravingcomprising the steps of

providing at least one chewing gum comprising tobacco alkaloid to auser,providing relief of nicotine craving to said user by transferring oftobacco alkaloid from the chewing gum to the human body of said user bychewing of said chewing gum,said chewing of said chewing gum comprising a chewing process involvinga transfer of tobacco alkaloid from said chewing gum above a thresholdtransfer rate in the period of about ½ minute to about 2½ minutes frominitiation of said chewing process.

According to the invention a transfer of nicotine or generally a tobaccoalkaloid is maintained at a threshold transfer rate in an intermediatephase of the chewing process thereby facilitating an advantageous andeffective fast relief due to the fact that transfer in this particularperiod affects the perception of nicotine and the resulting reliefsignificantly e.g. compared to transfer of nicotine late in the chewingprocess. It is especially noted that a desired “relief kick” accordingto the invention involves that a typically overlooked period of thechewing process, also referred to as the intermediate phase, provide avery significant part of the desirable nicotine dose to the human bodyas this particular period is within the typical time allocated to thesmoking of a cigarette.

According to the invention threshold transfer rate is understood as aminimum rate of nicotine transfer in a given time interval. In otherwords, transfer rates above this minimum rate may be applied within thescope of the invention. 2½ minutes corresponds to 150 seconds.

According to the invention it has been realised that one of the problemsrelated to the prior art is that a relief to the user of the chewing gumis hardly obtained or at least slowly when compared to the smoking of acigarette. It has also been realised that the provisions of the priorart related to this problem is typically concerned with the amount ofreleased nicotine from the chewing gum and basically not giving muchthought of how the actual transfer of nicotine is performed. This isboth the fact with respect to conventional long term release based on achewing time over approximately 30 minutes and the fast release ofnicotine in e.g. coating. Thus, it has been realised that a very fastrelease of nicotine, e.g. from the coating, over the first few secondsappears to have too little influence on the first five to ten minutes ofchewing due to the fact that a large part of this nicotine is swallowedand transferred to the blood merely metabolically.

According to the invention a transfer rate should be understood as atransfer rate of nicotine or tobacco alkaloid from the chewing gum tothe exterior, i.e. a release rate although the basic desired performanceof the chewing gum also includes a transfer from the chewing gum to theblood of the relevant human body. Such a release rate may e.g. bemeasured in sub-periods of 30 seconds.

In the present invention the term “tobacco alkaloid” mean nicotine ornicotine-like alkaloid such as nor-nicotine, lobeline, and the like, inthe free base or pharmacologically acceptable acid addition salt form.Plant alkaloids of this type are obtainable from species of Nicotianawhich is a source for nicotine and nor-nicotine, as well as species ofLobelia and Lobeliaceae (Indian tobacco) which are a source forlobeline.

Moreover, it is generally noted that specific examples and explanationspecifically referring to nicotine as active agent against craving in noway restricts the scope of the invention with respect to use of othertobacco alkaloids for the same specific purpose. A specific mentioningof nicotine at any place in this application is only used for thepurpose of exemplifying the invention in a tangible way and not for thepurpose of excluding alternative functionally equivalents.

It should generally be noted that nicotine is a preferred tobaccoalkaloid.

In the present invention, the term nicotine encompasses nicotine or anicotine derivative in any form such as, e.g. physical forms likeamorphous, crystalline, polymerphous etc. or chemical form like isomersand enantiomers etc. as well as any pharmaceutically acceptable salts,complex or solvate thereof. Nicotine may be selected from nicotine base,nicotine hydrochloride, nicotine dihydrochloride, nicotine monotartrate,nicotine bitartrate, nicotine sulfate, nicotine zinc chloride such aszinc chloride monohydrate and nicotine salicylate.

In an embodiment of the invention said tobacco alkaloid comprisesnicotine.

In an embodiment of the invention said transfer rate refer to a transferof nicotine from the chewing gum to the exterior of the chewing gum.

According to an advantageous embodiment of the invention, the chewingtime may be shortened significantly for at least two different reasons,first of all: a relief is obtained by the user relatively fast due tothe provisions of the invention and secondly: a mere maintenance ofnicotine in the blood appears to be a dynamic more than a stationaryprocess thereby rendering a mere continuous maintenance of nicotine lessdesirable to a user compared to a fast relied of initiated craving. Inother words, relief of craving appears to be a dynamic process.

In an embodiment of the invention said threshold transfer rate isevaluated in sub periods of the period of about ½ minute to about 2½minutes from initiation of said chewing process.

According to an embodiment of the invention, a sub period of 30 secondsmay be advantageous for the purpose of establishing whether the transferrate is maintained. A transfer rate measured in 30 seconds has thusproved sufficient for the purpose of obtaining a fast relief. Thus, whenapplying a sub period of 30 seconds, a transfer should comply withrequirements defined in four sub periods, namely the sub periods ½-1minute, 1-1½ minute, ½-2 minutes and 2-2½ minutes.

Evidently even transfer rates may be measured in shorter sub periods oftime, e.g. 15 seconds may be applied. Longer sub periods may also beapplied or sub periods of different length, although the period shouldbe chosen carefully for the purpose of avoiding lowering or dropouts ofthe nicotine or tobacco alkaloid transfer during the intermediaterelease. In particular, according to the invention, a dropout should beavoided in the intermediate transfer, i.e. from about ½ to 2½ minutes assuch a dropout inevitably would result in a lowered transfer in spite ofthe fact that a complete release of nicotine is high.

In an embodiment of the invention said chewing of said chewing gumcomprising a chewing process involving a transfer of tobacco alkaloidfrom said chewing gum above a further threshold transfer rate in theperiod of about 2½ minutes to about 10 minutes from initiation of saidchewing process, preferably in the period of about 2½ minutes to about 5minutes from initiation of said chewing process.

According to a further embodiment of the invention a further thresholdvalue may be applied for the chewing process after the initial 2½minutes of chewing. Thus, according to an advantageous embodiment of theinvention such threshold value should preferably ensure that arelatively high tobacco alkaloid transfer is obtained in the period from2½ minutes up to 10 or preferably at least 5 minutes.

In this way, maintenance of the initially obtained relief may beobtained.

In an embodiment of the invention said threshold transfer rate resultsin a release of at least 2%, preferably at least 2.5% of the tobaccoalkaloid comprised in said chewing gum prior to chewing, every 30seconds in the period from minutes to about 2½ minutes from initiationof said chewing process.

According to an embodiment of the invention, the tobacco alkaloidrelease of the chewing is at least 2%, preferably at least 2.5%, everythirty seconds thereby maintaining a high osmotic pressure on the mucosamembrane when chewing. This initial focussing on keeping tobaccoalkaloid constantly available in the mouth is in particular important inthe early phase of the chewing process due to the fact that a fastrelief to a user should preferably be obtained quite fast compared toconventional tobacco alkaloid containing chewing gum and that suchdesired fast relief requires not only just sporadic or late releasephases but a maintained constantly high availability of tobacco alkaloidin the mouth over at least a part of the period usually required forsmoking a cigarette.

In an embodiment of the invention said threshold transfer rate resultsin a release of at least 3%, preferably at least about 4% of the tobaccoalkaloid comprised in said chewing gum prior to chewing, every 30seconds in the period from about ½ minute to about 2½ minutes frominitiation of said chewing process.

According to an embodiment of the invention, the tobacco alkaloidrelease of the chewing is at least 3%, preferably at least 4%, everythirty seconds thereby maintaining a high osmotic pressure on the mucosamembrane when chewing. This initial focussing on keeping tobaccoalkaloid constantly available in the mouth is in particular important inthe early phase of the chewing process due to the fact that a fastrelief to a user should preferably be obtained quite fast compared toconventional tobacco alkaloid containing chewing gum and that suchdesired fast relief requires not only just sporadic or late releasephases but a maintained constantly high availability of tobacco alkaloidin the mouth over at least a part of the period usually required forsmoking a cigarette.

In an embodiment of the invention said threshold transfer rate resultsin a release of at least 5%, preferably at least about 6% of the tobaccoalkaloid comprised in said chewing gum prior to chewing, every 30seconds in the period from about ½ minute to about 2½ minutes frominitiation of said chewing process.

According to a further advantageous embodiment of the invention atransfer rate may be established and maintained at a high level therebyfeaturing an improved fast relief of the user.

In an embodiment of the invention said threshold transfer rate resultsin a release of at least 2%, preferably at least 3% of the tobaccoalkaloid comprised in said chewing gum prior to chewing, every 30seconds in the period of about 2½ minutes to about 5 minutes frominitiation of said chewing process.

According to a further advantageous embodiment of the invention, tobaccoalkaloid should also be kept available at high rate in the period ofabout 2½ to 5 minutes after initiation of the chewing process. Again, itshould be noted that such threshold rate should be complied with atvirtually anytime within the interval of 2.5 to 5 minutes frominitiation of the chewing process.

In an embodiment of the invention said threshold transfer rate resultsin a release of at least 3%, preferably at least 3.5% of the tobaccoalkaloid comprised in said chewing gum prior to chewing, every 30seconds in the period of about 2½ minutes to about 5 minutes frominitiation of said chewing process.

According to a further advantageous embodiment of the invention, tobaccoalkaloid should also be kept available at high rate in the period ofabout 2½ to 5 minutes after initiation of the chewing process. Again, itshould be noted that such threshold rate should be complied with atvirtually time within the interval of 2.5 to 5 minutes from initiationof the chewing process.

In an embodiment of the invention wherein said threshold transfer rateresults in a release of at least 4%, preferably at least 5% of thetobacco alkaloid comprised in said chewing gum prior to chewing, every30 seconds in the period of about 5 minutes to about 10 minutes frominitiation of said chewing process.

In an embodiment of the invention said threshold transfer rate resultsin a release of at least 2 to 10%, preferably at least 5% of the tobaccoalkaloid comprised in said chewing gum prior to chewing in the period ofabout 0 seconds to about 30 seconds from initiation of said chewingprocess.

In an embodiment of the invention said threshold transfer rate resultsin a release of less than 14%, preferably less than 12% of the tobaccoalkaloid comprised in said chewing gum prior to chewing in the period ofabout 0 seconds to about 2½ minutes from initiation of said chewingprocess.

According to an embodiment of the invention, the initial transfer oftobacco alkaloid from the chewing gum should be kept below 12 to 14% ofthe tobacco alkaloid comprised in the chewing gum prior to chewing inorder to avoid socalled burning or tingling. Moreover, too muchreleasing of e.g. nicotine would on the other hand result in that a partof the released nicotine is swallowed and therefore only effective by ametabolic transfer.

In an embodiment of the invention said threshold transfer rate resultsin a release of at most 18%, preferably at most 15% of the tobaccoalkaloid comprised in said chewing gum prior to chewing in the period ofabout 10 to about 30 minutes from initiation of said chewing process.

In an embodiment of the invention said threshold transfer rate resultsin a release of at least 0.03 mg, preferably at least 0.04 mg of thetobacco alkaloid comprised in said chewing gum prior to chewing, every30 seconds in the period from about 1 minute to about 2½ minutes frominitiation of said chewing process.

According to the invention a build-up of nicotine or tobacco alkaloid inthe blood should preferably be obtained by a maintained osmotic pressureon the mucous membrane of the mouth in the intermediate period of thechewing process, e.g. in the first ten minutes of the chewing process.

In an embodiment of the invention said threshold transfer rate resultsin a release of at least 0.05 mg, preferably at least 0.06 mg of thetobacco alkaloid comprised in said chewing gum prior to chewing, every30 seconds in the period from about 1 minute to about 2½ minutes frominitiation of said chewing process.

In an embodiment of the invention said threshold transfer rate resultsin a release of at least 0.08 mg, preferably at least 0.1 mg of thetobacco alkaloid comprised in said chewing gum prior to chewing, every30 seconds in the period from about 1 minute to about 2½ minutes frominitiation of said chewing process.

In an embodiment of the invention said threshold transfer rate resultsin a release of at least 0.03 mg, preferably at least 0.04 mg of thetobacco alkaloid comprised in said chewing gum prior to chewing, every30 seconds in the period of about 2½ to about 5 minutes from initiationof said chewing process.

In an embodiment of the invention said threshold transfer rate resultsin a release of at least 0.05 mg, preferably at least 0.06 mg of thetobacco alkaloid comprised in said chewing gum prior to chewing, every30 seconds in the period of about 2½ minutes to about 5 minutes frominitiation of said chewing process.

In an embodiment of the invention wherein said threshold transfer rateresults in a release of at least 0.08 mg, preferably at least 0.1 mg ofthe tobacco alkaloid comprised in said chewing gum prior to chewing,every 30 seconds in the period of about 2½ minutes to about 5 minutesfrom initiation of said chewing process.

In an embodiment of the invention at least 0.5 mg of tobacco alkaloid isreleased within the initial 10 minutes of the chewing process orpreferably within the initial 5 to 8 minutes of the chewing process.

According to an embodiment of the invention even higher release shouldbe obtained such as at least 0.8 mg of tobacco alkaloid is releasedwithin the initial 10 minutes of the chewing process or preferablywithin the initial 5 to 8 minutes of the chewing process.

In an embodiment of the invention wherein different parts of the chewinggum is targeted tobacco alkaloid transfer at different times or indifferent periods of the chewing process.

According to an embodiment of the invention different parts of thechewing gum may be targeted tobacco alkaloid transfer at different timesor in different periods of the chewing process, thereby facilitating theobtaining of the desired constant transfers or at least the desiredminimum transfer of the relevant period of the chewing process, i.e.typically during the first three to five minutes of the chewing process.Thus, e.g. the very initial transfer of tobacco alkaloid, i.e. the firstseconds of the chewing process, may be increased by means of e.g.nicotine containing coating. Alternatively, nicotine may be comprised inbeads or other release-delaying means. Again, further means may includemixture of different polymers having different release properties.Further means may include different types of buffering.

Thus the threshold transfer rate is obtained by a combination ofdifferent parts of the chewing having different release profiles.

In an embodiment of the invention wherein said chewing gum comprising acoating and wherein said coating comprises tobacco alkaloid.

According to an embodiment of the invention, tobacco alkaloid iscomprised in the coating and may therefore be released quite fast in thevery early stage of the chewing process.

In an embodiment of the invention said chewing gum comprisessubstantially hydrophilic polymers.

In an embodiment of the invention the variation of transfer rate isminimized.

According to an embodiment of the invention, the significant variationsof tobacco alkaloid over time should be avoided in order to obtain anadvantageous taste masking. A sudden tobacco alkaloid peak would thus bedifficult to taste mask, especially when dealing with peaks occurringsubsequently to the very initial chewing process. I1 and I3 as describedbelow are examples of such smoothed release.

In an embodiment of the invention wherein said tobacco alkaloid iscomprised in a ion exchange resin.

According to an embodiment tobacco alkaloid is nicotine polacrilex.

In an embodiment of the invention wherein said tobacco alkaloidcomprises salts of nicotine.

In an embodiment of the invention said tobacco alkaloid comprisesnicotine in its free from.

In an embodiment of the invention the tobacco alkaloid is buffered.

In an embodiment of the invention the chewing process is less than 30minutes, preferably less than 20 minutes.

According to an embodiment the chewing process should be kept short inorder to comply with the basic principles of fast relief as obtained bythe desired emulation of the smoking process.

In an embodiment of the invention the chewing process is matching thesmoking time of a cigarette.

In an embodiment of the invention said chewing gum comprises a polymersystem in an amount of from about 2 to about 99% by weight, flavour inan amount of about 0.001 to about 30% by weight and sweeteners in anamount of about 2% to about 80% by weight.

In an embodiment of the invention said chewing gum comprises fillers inan amount of from about 0 to about 60% by weight, flavour in an amountof about 0.001 to about 30% by weight and sweeteners in an amount ofabout 2 to about 80% by weight.

In an embodiment of the invention said chewing gum comprises highintensity sweeteners in an amount of from about 0.001 to about 3% byweight and flavour in an amount of about 0.001 to about 30% by weight.

In an embodiment of the invention said polymer system compriseselastomers in an amount of about 0.1 to about 40% by weight of thechewing gum, preferably in an amount of about 2 to about 10% by weightof the chewing gum.

In an embodiment of the invention said polymer system compriseselastomer plasticizers in an amount of about 2 to about 60% by weight ofthe chewing gum, preferably in an amount of about 5 to about 30% byweight of the chewing gum.

In an embodiment of the invention said polymer system comprises wax inan amount of about 0 to about 30% by weight of the chewing gum,preferably in an amount of about 0 to about 15% by weight of the chewinggum.

In an embodiment of the invention said polymer system comprisessofteners in an amount of about 2 to about 30% by weight of the chewinggum, preferably in an amount of about 5 to about 20% by weight of thechewing gum.

In an embodiment of the invention said polymer system comprises fillersin an amount of about 0 to about 50% by weight of the chewing gum,preferably in an amount of about 0 to about 30% by weight of the chewinggum.

In an embodiment of the invention said polymer system comprisesantioxidants in an amount of about 0 to about 5% by weight of thechewing gum, preferably in an amount of about 0 to about 2% by weight ofthe chewing gum.

In an embodiment of the invention at least one piece of said chewing gumis chewed at a time.

In an embodiment of the invention at least two pieces of said chewinggum are chewed at a time.

In an embodiment of the invention at least one piece of said chewing gumis chewed a day.

In an embodiment of the invention at least one piece of said chewing gumis chewed when the person craves for nicotine.

According to an advantageous embodiment of the invention a tobaccoalkaloid holding chewing may even be applied solely as a reaction oncraving of a user. In other words, mere maintenance of a high nicotinelevel in the blood may be avoided.

In an embodiment of the invention at least one piece of said chewing ischewed when the person needs treatment including tobacco alkaloid ornicotine.

THE FIGURES

The invention will now be described with reference to the drawings ofwhich

FIG. 1 shows the release profile of prior art nicotine chewing gums,

FIG. 2 shows a break-up of the release in 30-second intervals of theintermediate release of prior art nicotine chewing gums,

FIG. 3 shows a break-up of the release in 30 second intervals of theintermediate release of nicotine chewing gums applied according to theinvention, and

FIG. 4 shows a release profile of a combination of prior art chewinggums and chewing gums according to the invention.

DETAILED DESCRIPTION OF THE INVENTION

In general, a chewing gum composition typically comprises awater-soluble bulk portion, a water-insoluble chewable gum base portionand flavouring agents. The water-soluble portion dissipates with aportion of the flavouring agent over a period of time during chewing.The gum base portion is retained in the mouth throughout the chew. Theterm chewing gum refers to both a chewing and bubble type gum in itsgeneral sense.

The gum base is the masticatory substance of the chewing gum, whichimparts the chew characteristics to the final product. The gum basetypically defines the release profile of flavours and sweeteners andplays a significant role in the gum product.

The insoluble portion of the gum typically may contain any combinationof elastomers, vinyl polymers, elastomer plasticizers, waxes, softeners,fillers and other optional ingredients such as colourants andantioxidants.

The composition of gum base formulations can vary substantiallydepending on the particular product to be prepared and on the desiredmasticatory and other sensory characteristics of the final product.However, typical ranges (% by weight) of the above gum base componentsare: 5 to 50% by weight elastomeric compounds, 5 to 55% by weightelastomer plasticizers, 0 to 40% by weight of waxes, 5 to 35% by weightsoftener, 0 to 50% by weight filler, and 0 to 5% by weight ofmiscellaneous ingredients such as antioxidants, colourants, etc.

Function of Elastomers

Elastomers provide the rubbery, cohesive nature to the gum, which variesdepending on this ingredient's chemical structure and how it may becompounded with other ingredients. Elastomers suitable for use in thegum base and gum of the present invention may include natural orsynthetic types.

Elastomers

The elastomer may be any water-insoluble polymer known in the art, andincludes those gum polymers utilized for chewing gum and bubble gumlisted in Food and Drug Administration, CFR, Title 21, Section 172,615,as “Masticatory Substances of Natural Vegetable Origin” and “MasticatorySubstances, Synthetic”

Useful natural elastomers include natural rubber such as smoked orliquid latex and guayule, natural gums such as jelutong, lechi caspi,perillo, sorva, massaranduba balata, massaranduba chocolate, nispero,rosidinha, chicle, gutta percha, gutta kataiu, niger gutta, tunu,chilte, chiquibul, gutta hang kang.

Useful synthetic elastomers include high molecular weight elastomerssuch as butadiene-styrene copolymers, polyisobutadiene andisobutylene-isoprene copolymers, low molecular weight elastomers such aspolybutene, polybutadiene and polyisobutylene, vinyl polymericelastomers such as polyvinyl acetate, polyethylene, vinyl copolymericelastomers such as vinyl acetate/vinyl laurate, vinyl acetate/vinylstearate, ethylene/vinyl acetate, polyvinyl alcohol or mixtures thereof.

Butadiene-styrene type elastomers, or SBR as they may be called,typically are copolymers of from about 20:80 to 60:40 styrenes:butadienemonomers. The ratio of these monomers affects the elasticity of the SBRas evaluated by mooney viscosity. As the styrene:butadiene ratiodecreases, the mooney viscosity decreases.

The structure of SBR typically consists of straight chain 1,3-butadienecopolymerized with phenylethylene (styrene) and provides the non-linearmolecular nature of these elastomers. The average molecular weight ofSBR is <600.000 g/mole.

Isobutylene-isoprene type elastomers, or butyl as they may be called,have molar percent levels of isoprene ranging from 0.2 to 4.0. Similarto SBR, as the isoprene:isobutylene ratio decreases, so does theelasticity, measured by mooney viscosity.

The structure of butyl rubber typically consists of branched2-methyl-1,3-butadiene (isoprene) copolymerized with branched2-methylpropene (isobutylene), and, as with SBR, this type of structureis non-linear in nature. The average molecular weight of SBR is in therange from 150.000 g/mole to 1.000.000 g/mole.

Polyisobutylene, or PIB as they may be called, type elastomers arepolymers of 2-methylpropene and, as with SBR and butyl, are non-linearin nature. The low molecular weight elastomers provide soft chewcharacteristics to the gum base and still provide the elastic qualitiesas do the other elastomers. Average molecular weights may range fromabout 30,000 to 120,000 g/mole and the penetration may range from about4 millimetres to 20 millimetres. The higher the penetration, the softerthe PIB. Similar to the SBR and butyl, the high molecular weightelastomers provide elasticity the gum. Average molecular weight mayrange from 120.000 to 1.000.000 g/mole.

Polybutenes range in average molecular weight from about 5.000 g/mole toabout 30.000 g/mole.

Function of Vinyl Polymers

Vinyl polymeric and copolymeric type elastomers provide tack resistance,vary the chew characteristics of gums made from these bases having vinylpolymers and offer hydrophilic properties beneficial to sensoryperception of the final gums.

Vinyl Polymers

For vinyl copolymeric types, the amount of vinyl laurate, vinylstearate, or ethylene present in the vinyl laurate/vinyl acetate (L/VA),vinyl stearate/vinyl acetate (VS/VA), or ethylene/vinyl acetate (EVA)copolymers respectively typically ranges from about 10 to about 60% byweight of the copolymer. Average molecular weights of these polymers mayrange from about 2.000 g/mole to about 100,000 g/mole.

The vinyl polymers such as polyvinyl alcohol and polyvinyl acetate havean average molecular weight from about 8.000 g/mole to about 65.000g/mole.

Polymers of vinyl acetate (PVAc) are branched in nature. The degree ofbranching is increased when vinyl acetate monomers are copolymerizedwith vinyl laurate, vinyl stearate, ethylene and the like. The higherthe degree of branching, the higher the compatibility when blended orcompounded with normal-alkanic and iso-alkanic type waxes.

It is e.g. common in the industry to combine in a gum base a syntheticelastomer having a high molecular weight and a low-molecular-weightelastomer. Presently preferred combinations of synthetic elastomersinclude, but are not limited to, polyisobutylene and styrene-butadiene,polyisobutylene and polyisoprene, polyisobutylene andisobutylene-isoprene copolymer (butyl rubber) and a combination ofpolyisobutylene, styrene-butadiene copolymer and isobutylene isoprenecopolymer, and all of the above individual synthetic polymers inadmixture with polyvinyl acetate, vinyl acetate-vinyl lauratecopolymers, respectively and mixtures thereof.

Function of Elastomer Plasticizers

Elastomer plasticizers vary the firmness of the gum base. Theirspecificity on elastomer inter-molecular chain breaking (plasticizing)along with their varying softening points cause varying degrees offinished gum firmness and compatibility when used in base. This may beimportant when one wants to provide more elastomeric chain exposure tothe alkanic chains of the waxes.

Elastomer Plasticizers

Elastomer plasticizers suitable for use in the present invention includenatural rosin esters often referred to as ester gums. Such elastomerplasticizers known in the art are methyl, glycerol and pentaerythritolesters of rosins and modified rosins, such as hydrogenated, dimerizedand polymerized rosins. Examples are glycerol ester of wood and gumrosin, glycerol ester of partially hydrogenated wood and gum rosin,glycerol ester of polymerized wood and gum rosin, glycerol ester ofpartially dimerized wood and gum rosin, glycerol ester of tall oilrosin, pentaerytritol ester of wood and gum rosin, pentaerythritolesters of partially and fully hydrogenated wood and gum rosin, methylesters of wood and gum rosins and partially and fully hydrogenatedmethyl esters of wood and gum rosin.

The synthetic elastomer plasticizers include terpene resins derived fromalpha-pinene, beta-pinene and/or d-limonene.

The elastomer plasticizers used may be of one type or of combinations ofmore than one type. Typically, the ratios of one to the other aredependent on each respective softening point, the effect on flavourrelease, and the respective degree of tack they case to the gum. Balland ring softening points of the rosin ester types described above mayrange from about 45.degree. C. to about 120.degree. C. Softening pointsof the terpene resins may range from about 60.degree. C. to about130.degree. C.

Function of Waxes

Petroleum waxes aid in the curing of the finished gum made from the gumbase as well as improve shelf life and texture. Wax crystal sizeinfluences the release of flavour. Those waxes high in iso-alkanes havea smaller crystal size than those waxes high in normal-alkanes,especially those with normal-alkanes of carbon numbers less than 30. Thesmaller crystal size allows slower release of flavour since there ismore hindrance of the flavour's escape from this wax versus a wax havinglarger crystal sizes. The compatibility of gum bases made usingnormal-alkanic waxes is less when compared to gum bases made withiso-alkanic waxes.

Waxes

Petroleum wax (refined paraffin and microcrystalline wax) and paraffinwax are composed of mainly straight-chained normal-alkanes and branchediso-alkanes. The ratio of normal-alkanes to iso-alkanes varies.

The normal-alkanic waxes typically have carbon chain lengths >C-18 butthe lengths are not predominantly longer than C-30. The branched andring structures are located near the end of the chain for those waxesthat are predominantly normal-alkanic. The viscosity of normal-alkanicwaxes is <10 mm2/s (at 100° C.) and the combined number averagemolecular weight is <600 g/mole.

The iso-alkanic waxes typically have carbon lengths that arepredominantly greater than C-30. The branched chains and ring structuresare located randomly along the carbon chain in those waxes that arepredominantly iso-alkanic. The viscosity of iso-alkanic waxes is greaterthan 10 mm2/s (at 100° C.) and the combined number average molecularweight is >600 g/mole.

Synthetic waxes are produced by means that are atypical for petroleumwax production and are thus not considered petroleum wax. The syntheticwaxes may include waxes containing branched alkanes and copolymerizedwith monomers such as, but not limited to propylene, polyethylene, andFischer Tropsch type waxes. Polyethylene wax is a synthetic waxcontaining alkane units of varying lengths having attached theretoethylene monomers.

The natural waxes may include rice bran wax, bees' wax, carnauba wax orcandelilla wax.

The waxes may be used alone or in any combination.

Function of Softeners

The selection of softeners has an influence on the softness of the base.Softeners modify the texture, cause the hydrophobic and hydrophiliccomponents of the base to be miscible, and may further plasticize thesynthetic elastomers of the gum base. The emulsifiers, which belongs tothe group of softeners, provide the gum base with water-bindingproperties, which confer to the gum base a pleasant smooth surface andreduce its adhesive properties.

Softeners

Softeners suitable for use in the gum base include triglycerides ofnon-hydrogenated, partially hydrogenated and fully hydrogenatedvegetable oils and tallow, cocoa butter and degreased cocoa powder andin addition to these the emulsifiers.

The group of triglycerides include cottonseed, palm, palm kernel,coconut, safflower, rapeseed, sunflower, tallow, soybean, cocoa butter,medium-chained triglycerides and the like.

The caproic, caprylic, capric, myristic, lauric and palmitic fatty acidsof the triglycerides tend to plasticize the synthetic elastomers morethan triglycerides containing predominantly stearic fatty acid

To the group of emulsifiers belong the monoglycerides, diglycerides,acetylated mono and diglycerides, distilled mono- and diglycerides,glycerol monostearate, propylene glycol monostearate, Na-, K-, Mg- andCa-stearates, glycerol triacetate, fatty acid monoglycerides (e.g.stearic, palmitic, oleic and linoleic acids), lactic acid esters andacetic acid esters of mono- and diglycerides, sugar esters of ediblefatty acids also referred to as sucrose polyesters including thosedisclosed in WO 00/25598, lecithin and hydroxylated lecithin, most ofthese may contain triglyceride levels less than 2% by weight from theirmanufacturing processing,

The softeners including the emulsifiers may be used alone or at leasttwo or more in combination.

Function of Fillers

Fillers used in gum base modify the texture of the gum base and aid inprocessing. Particle size has an effect on cohesiveness, density andprocessing characteristics of the gum base and its compounding. Thesmaller the particle size, the more dense and cohesive the final gumbase. Also, by selecting fillers based on their particle sizedistribution, initial mass compounding may be varied, thus allowingalteration of the compounding characteristics of the initial mass duringgum base processing and ultimately the final chew characteristics ofgums made from these gum bases.

Fillers

Fillers suitable for use in the gum base include magnesium and calciumcarbonate, ground limestone and silicate types such as magnesium andaluminum silicate, kaolin and clay, aluminium oxide, silicium oxide,talc, as well as titanium oxide, mono-, di- and tricalcium phosphate,sodium sulphate, cellulose polymers such as ethyl, methyl and wood ormixtures thereof.

Talc filler may be used in the gum base and gum of the present inventionthat may come in contact with or employ acid flavours or provide anacidic environment needed to prevent degradation of an artificialsweetener by reacting with calcium carbonate type fillers. Mean particlesize for calcium carbonate and talc fillers typically range from about0.1 micron to about 15 microns.

The fillers may also include natural organic fibres such as fruitvegetable fibres, grain, rice, cellulose and combinations thereof.

Function and List of Other Optional Ingredients Such as Antioxidants,Colourants and Flavourants:

Antioxidants prolong shelf life and storage of gum base, finished gum ortheir respective components including fats and flavour oils.

Antioxidants suitable for use in gum base include butylatedhydroxyanisole (BHA), butylated hydroxytoluene (BHT), betacarotenes,tocopherols, acidulants such as Vitamin C, propyl gallate, othersynthetic and natural types or mixtures thereof.

Flavourants and colourants impart characteristics or remove or maskundesired characteristics. Colourants may typically include FD&C typelakes, plant extracts, fruit and vegetable extracts and titanium dioxideflavourants may typically include cocoa powder, heat-modified aminoacids and other vegetable extracts.

Preparation of Gum Bases

Gum bases are typically prepared by adding an amount of the elastomer,elastomer plasticizer and filler, and on occasion a vinyl polymer, to aheated (10° C.-120° C.) sigma blade mixer with a front to rear speedratio of from about 1.2:1 to about 2:1, the higher ratio typically beingused for gum base which requires more rigorous compounding of itselastomers.

The initial amounts of ingredients comprising the initial mass may bedetermined by the working capacity of the mixing kettle in order toattain a proper consistency and by the degree of compounding desired tobreak down the elastomer and increase chain branching. The higher thelevel of filler at the start or selection of a filler having a certainparticle size distribution, the higher the degree of compounding andthus more of the elastomeric chain crosslinking are broken, causing morebranching of the elastomer thus lower viscosity gum bases and thussofter final gum base and gum made from such a gum base. The longer thetime of compounding, the use of lower molecular weight or softeningpoint gum base ingredients, the lower the viscosity and firmness of thefinal gum base.

Compounding typically begins to be effective once the ingredients havemassed together. Anywhere from 15 minutes to 90 minutes may be thelength of compounding time.

Preferably, the time of compounding is from 20 minutes to about 60minutes. The amount of added elastomer plasticizer depends on the levelof elastomer and filler present. If too much elastomer plasticizer isadded, the initial mass becomes over plasticized and not homogeneous.

After the initial ingredients have massed homogeneously and compoundedfor the time desired, the balance of the gum base ingredients are addedin a sequential manner until a completely homogeneous molten mass isattained. Typically, any remainder of elastomer, elastomer plasticizer,vinyl polymer and filler, are added within 60 minutes after the initialcompounding time. The filler and the elastomer plasticizer wouldtypically be individually weighed and added in portions during thistime. The optional waxes and the softeners are typically added after theelastomer and elastomer plasticizers and during the next 60 minutes.Then the mass is allowed to become homogeneous before dumping.

Typical gum base processing times may vary from about one to about threehours, preferably from about 1½ to 2½ hours, depending on theformulation. The final mass temperature when dumped may be between 70°C. and 130° C. and preferably between 100° C. and 120° C. The completedmolten mass is emptied from the mixing kettle into coated or lined pans,extruded or cast into any desirable shape and allowed to cool andsolidify. Those skilled in the art will recognize that many variationsof the above described procedure may be followed.

The Water-Soluble Portion of Chewing Gum.

The water-soluble portion of the chewing gum may comprise softeners,sweeteners, high intensity sweeteners, flavoring agents, acidulants,fillers, antioxidants, and other components that provide desiredattributes. Softeners typically constitute from about 0.5 percent toabout 25.0 percent by weight of the chewing gum. The bulking agentsgenerally comprise from about 5 percent to about 90 percent, preferablyfrom about 20 percent to about 80 percent of the chewing gum.High-intensity sweeteners in gum typically may range from about 0.01 to0.50 weight percent. A flavoring agent may be present in the chewing gumin an amount within the range of from about 0.1 to about 30.0 weightpercent of the gum.

Softeners

Softeners are added to the chewing gum in order to optimize thechewability and mouth feel of the gum.

Softeners contemplated for use in the gum include glycerin, modifiedlecithin and combinations thereof. Further aqueous sweetener solutionssuch as those containing sorbitol, hydrogenated starch hydrolysates,corn syrup and combinations thereof may be used as softeners.

Sweeteners

Bulk sweeteners include both sugar and sugarless components. Bulksweeteners may typically constitute 5 to about 95% by weight of thechewing gum, more typically constitute 20 to about 80% by weight, andmore commonly, 30 to 60% by weight of the gum.

The sweeteners often fill the role of bulking agents in the gum. Thesweeteners are improving juiciness of the gum and are supporting theflavour profile of the gum. Sugar sweeteners generally include, but arenot limited to saccharide-containing components commonly known in thechewing gum art, such as sucrose, dextrose, maltose, saccharose,lactose, sorbose, dextrin, trehalose, D-tagatose, dried invert sugar,fructose, levulose, galactose, corn syrup solids, glucose syrup,hydrogenated glucose syrup, and the like, alone or in combination.

The sweetener can be used in combination with sugarless sweeteners.

Generally, sugarless sweeteners include components with sweeteningcharacteristics but which are devoid of the commonly known sugars andcomprise, but are not limited to, sugar alcohols such as sorbitol,mannitol, xylitol, hydrogenated starch hydrolyzates, maltitol, isomalt,erythritol, lactitol and the like, alone or in combination.

Depending on the particular sweetness release profile and shelf-lifestability needed, bulk sweeteners can also be used in combinationhigh-intensity sweeteners. Preferred high intensity sweeteners include,but are not limited to sucralose, aspartame, salts of acesulfame,alitame, saccharin and its salts, cyclamic acid and its salts,cyclamate, glycyrrhizin, dihydrochalcones, thaumatin, monellin,sterioside and the like, alone or in combination. In order to providelonger lasting sweetness and flavour perception, it may be desirable toencapsulate or otherwise control the release of at least a portion ofthe artificial sweetener. Such techniques as wet granulation, waxgranulation, spray drying, spray chilling, fluid bed coating,coascervation, encapsulation in yeast cells and fibre extrusion may beused to achieve the desired release characteristics. The encapsulationcan also be performed in another material such as resin.

Usage level of the artificial sweetener will vary greatly and willdepend on such factors as potency of the sweetener, rate of release,desired sweetness of the product, level and type of flavour used andcost considerations. Thus, the active level of artificial sweetener mayvary from 0.02 to about 8%. When carriers used for encapsulation areincluded, the usage level of the encapsulated sweetener will beproportionally higher.

Combinations of sugar and/or sugarless sweeteners may be used in chewinggum.

Additionally, the softener may also provide additional sweetness, ifsuch softeners as aqueous sugar or alditol are used.

If a low calorie gum is desired, a low caloric bulking agent can beused. Examples of low caloric bulking agents include polydextrose;Raftilose, Raftilin; Fructooligosaccharides (NutraFlora@); Palatinoseoligosaccharide; Guar Gum Hydrolysate (SunFiber@); or indigestibledextrin (Fibersol). However, other low calorie-bulking agents can beused.

Flavour

The chewing gum centres provided herein may contain aroma agents andflavouring agents including natural and synthetic flavourings e.g. inthe form of natural vegetable components, essential oils, essences,extracts, powders, including acids and other substances capable ofaffecting the taste profile. Examples of liquid and powdered flavouringsinclude coconut, coffee, chocolate, vanilla, grape fruit, orange, lime,menthol, liquorice, caramel aroma, honey aroma, peanut, walnut, cashew,hazelnut, almonds, pineapple, strawberry, raspberry, tropical fruits,cherries, cinnamon, peppermint, wintergreen, spearmint, eucalyptus, andmint, fruit essence such as from apple, pear, peach, strawberry,apricot, raspberry, cherry, pineapple, and plum essence. The essentialoils include peppermint, spearmint, menthol, eucalyptus, clove oil, bayoil, anise, thyme, cedar leaf oil, nutmeg, and oils of the fruits (e.g.lemon, bergamot and orange) as mentioned above.

The chewing gum flavour may be a natural flavouring agent, which isfreeze-dried, preferably in the form of a powder, slices or pieces ofcombinations thereof. The particle size may be less than 3 mm,preferably less than 2 mm, more preferably less than 1 mm, calculated asthe longest dimension of the particle. The natural flavouring agent maybe in a form where the particle size is from about 3 μm to 2 mm, such asfrom 4 μm to 1 mm. Preferred natural flavouring agents include seedsfrom a fruit e.g. from strawberry, blackberry and raspberry.

Various synthetic flavours, such as mixed fruit flavours may also beused in the present chewing gum centres. The aroma agent may be used inquantities smaller than those conventionally used. The aroma agentsand/or flavours may be used in an amount of from 0.01 to about 30% byweight (preferably from 0.01 to about 15% by weight) of the finalproduct depending on the desired intensity of the aroma and/or flavourused. Preferably, the content of aroma/flavour is in the range of from0.2 to 3% by weight of the total composition.

Acidulants

Also various acids are used typically in combination with fruitflavours, such as adipinic acid, succinic acid, fumaric acid, citricacid, tartaric acid, malic acid, acetic acid, lactic acid, phosphoricacid and glutaric acid or salts thereof. They are typically added inamounts of 0.01 to 10%.

Fillers

Fillers suitable for use in the chewing gum include magnesium andcalcium carbonate, ground limestone and silicate types such as magnesiumand aluminum silicate, kaolin and clay, aluminium oxide, silicium oxide,talc, as well as titanium oxide, mono-, di- and tricalcium phosphate,sodium sulphate, cellulose polymers such as ethyl, methyl and wood ormixtures thereof.

Talc filler may be used in the chewing gum of the present invention thatmay come in contact with or employ acid flavours or provide an acidicenvironment needed to prevent degradation of an artificial sweetener byreacting with calcium carbonate type fillers. Mean particle size forcalcium carbonate and talc fillers typically range from about 0.1 micronto about 15 microns.

The fillers may also include natural organic fibres such as fruitvegetable fibres, grain, rice, cellulose and combinations thereof.

Function and List of Other Ingredients Such as Antioxidants, Colourantsand Taste Masking Agents:

Antioxidants prolong shelf life and storage of gum base, finished gum ortheir respective components including fats and flavour oils.

Antioxidants

Antioxidants suitable for use in gum base include butylatedhydroxyanisole (BHA), butylated hydroxytoluene (BHT), betacarotenes,tocopherols, acidulants such as Vitamin C, propyl gallate, othersynthetic and natural types or mixtures thereof.

Colourants

Colourants and whiteners may include FD & C-type dyes and lakes, fruitand vegetable extracts, titanium dioxide, and combinations thereof.

Taste Masking Agents

The taste masking agent improves the organoleptic properties of theproduct.

The masking agent include sucralose, zinc gluconate, ethyl maltol,glycine, acesulfame-K, aspartame, saccharin, fructose, xylitol, spraydried licorice root, glycerrhizine, dextrose, sodium gluconate, gluconodelta-lactone, ethyl vanillin, vanillin, normal and high-potencysweeteners, and a variety of appropriate flavors.

Active Agents

The chewing gum according to the present invention may also compriseactive agents other than nicotine. Active agents to be used inconnection with the present invention may be any substance desired to bereleased from the chewing gum. If an accelerated rate of release isdesired, corresponding to the effect obtained for the flavour, theprimary substances are those with limited water solubility, typicallybelow 10 g/100 ml including substances, which are entirely waterinsoluble. Examples are medicines, dietary supplements, oralcompositions, anti-smoking agents, highly potent sweeteners, pHadjusting agents, etc.

Further examples of active ingredients include paracetamol, benzocaine,cinnarizine, menthol, carvone, coffeine, chlorhexidine-di-acetate,cyclizine hydrochloride, 1,8-cineol, nandrolone, miconazole, mystatine,aspartame, sodium fluoride, nicotine, saccharin, cetylpyridiniumchloride, other quaternary ammonium compounds, vitamin E, vitamin A,vitamin D, glibenclamide or derivatives thereof, progesterone,acetylsalicylic acid, dimenhydrinate, cyclizine, metronidazole, sodiumhydrogencarbonate, the active components from ginkgo, the activecomponents from propolis, the active components from ginseng, methadone,oil of peppermint, salicylamide, hydrocortisone or astemizole.

Examples of active agents in the form of dietary supplements are forinstance salts and compounds having the nutritive effect of vitamin B2(riboflavin), B12, folinic acid, niacine, biotine, poorly solubleglycerophosphates, amino acids, the vitamins A, D, E and K, minerals inthe form of salts, complexes and compounds containing calcium,phosphorus, magnesium, iron, zinc, copper, iodine, manganese, chromium,selenium, molybdenum, potassium, sodium or cobalt.

Furthermore, reference is made to lists of nutrients accepted by theauthorities in different countries such as for instance US code ofFederal Regulations, Title 21, Section 182.5013.182 5997 and182.8013-182.8997.

Examples of active agents in the form of compounds for the care ortreatment of the oral cavity and the teeth, are for instance boundhydrogen peroxide and compounds capable of releasing urea duringchewing.

Examples of active agents in the form of antiseptics are for instancesalts and compounds of guanidine and biguanidine (for instancechlorhexidine diacetate) and the following types of substances withlimited water-solubility: quaternary ammonium compounds (for instanceceramine, chloroxylenol, crystal violet, chloramine), aldehydes (forinstance paraformaldehyde), compounds of dequaline, polynoxyline,phenols (for instance thymol, para chlorophenol, cresol)hexachlorophene, salicylic anilide compounds, triclosan, halogenes(iodine, iodophores, chloroamine, dichlorocyanuric acid salts), alcools(3,4 dichlorobenzyl alcohol, benzyl alcohol, phenoxyethanol,phenylethanol), cf. furthermore Martindale, The Extra Pharmacopoeia,28th edition, page 547-578; metal salts, complexes and compounds withlimited water-solubility, such as aluminium salts, (for instancealuminium potassium sulfate AIK (S04) 2, 12H20) and furthermore salts,complexes and compounds of boron, barium, strontium, iron, calcium,zinc, (zinc acetate, zinc chloride, zinc gluconate), copper (copperchloride, copper sulfate), lead, silver, magnesium, sodium, potassium,lithium, molybdenum, vanadium should be included; other compositions forthe care of mouth and teeth: for instance; salts, complexes andcompounds containing fluorine (such as sodium fluoride,sodiummonofluorophosphate, aminofluorides, stannous fluoride),phosphates, carbonates and selenium.

Cf. furthermore J. Dent. Res. Vol. 28 No. 2, page 160-171, 1949, whereina wide range of tested compounds are mentioned.

Examples of active agents in the form of agents adjusting the pH in theoral cavity include for instance: acceptable acids, such as adipinicacid, succinic acid, fumaric acid, or salts thereof or salts of citricacid, tartaric acid, malic acid, acetic acid, lactic acid, phosphoricacid and glutaric acid and acceptable bases, such as carbonates,hydrogen carbonates, phosphates, sulfates or oxides of sodium,potassium, ammonium, magnesium or calcium, especially magnesium andcalcium.

Examples of active agents in the form of anti-smoking agents include forinstance: nicotine, tobacco powder or silver salts, for instance silveracetate, silver carbonate and silver nitrate.

Further examples of active agents are medicines of any type.

Examples of active agents in the form of medicines include coffeine,salicylic acid, salicyl amide and related substances (acetylsalicylicacid, choline salicylate, magnesium salicylate, sodium salicylate),paracetamol, salts of pentazocine (pentazocine hydrochloride andpentazocinelactate), buprenorphine hydrochloride, codeine hydrochlorideand codeine phosphate, morphine and morphine salts (hydrochloride,sulfate, tartrate), methadone hydrochloride, ketobemidone and salts ofketobemidone (hydrochloride), beta-blockers, (propranolol), calciumantagonists, verapamil hydrochloride, nifedinpine as well as suitablesubstances and salts thereof mentioned in Pharm. Int., Nov. 85, pages267-271, Barney H. Hunter and Robert L. Talbert, nitroglycerine,erythrityl tetranitrate, strychnine and salts thereof, lidocaine,tetracaine hydrochloride, etorphine hydrochloride, atropine, insulin,enzymes (for instance papain, trypsin, amyloglucosidase. glucoseoxidase,streptokinase, streptodornase, dextranase, alpha amylase), polypeptides(oxytocin, gonadorelin, (LH. RH), desmopressin acetate (DDAVP),isoxsuprine hydrochloride, ergotamine compounds, chloroquine (phosphate,sulfate), isosorbide, demoxytocin, heparin.

Other active ingredients include beta-lupeol, Letigen, Sildenafilcitrate and derivatives thereof.

Dental products include Carbami, CPP Caseine Phospho Peptide;Chlorhexidine, Chlorhexidine di acetate, Chlorhexidine Chloride,Chlorhexidine di gluconate, Hexetedine, Strontium chloride, PotassiumChloride, Sodium bicarbonate, Sodium carbonate, Fluor containingingredients, Fluorides, Sodium fluoride, Aluminium fluoride, Ammoniumfluoride, Calcium fluoride, Stannous fluoride, Other fluor containingingredients Ammonium fluorosilicate, Potassium fluorosilicate, Sodiumfluorosilicate, Ammonium monofluorphosphate, Calcium monofluorphosphate,Potassium monofluorphosphate, Sodium monofluorphosphate, OctadecentylAmmonium fluoride, Stearyl Trihydroxyethyl PropylenediamineDihydrofluoride, Vitamins include A, B1, B2, B6, B12, Folin acid,niacin, Pantothensyre, biotine, C, D, E, K.

Minerals include Calcium, phosphor, magnesium, iron, Zink, Cupper, lod,Mangan, Crom, Selene, Molybden. Other active ingredients include: Q10@,enzymes. Natural drugs including Ginkgo Biloba, ginger, and fish oil.The invention also relates to use of migraine drugs such as Serotoninantagonists: Sumatriptan, Zolmitriptan, Naratriptan, Rizatriptan,Eletriptan; nausea drugs such as Cyclizin, Cinnarizin, Dimenhydramin,Difenhydrinat; hay fever drugs such as Cetrizin, Loratidin, pain reliefdrugs such as Buprenorfin, Tramadol, oral disease drugs such asMiconazol, Amphotericin B, Triamcinolonaceton; and the drugs Cisaprid,Domperidon, Metoclopramid.

Preparation of Chewing Gum

In general, chewing gum may be manufactured by sequentially adding thevarious chewing gum ingredients to a commercially available mixer knownin the art. After the initial ingredients have been thoroughly mixed,the gum mass is discharged from the mixer and shaped into the desiredform such as by rolling into sheets and cutting into sticks, extrudedinto chunks or casting into pellets.

Generally, the ingredients may be mixed by first melting the gum baseand adding it to the running mixer. Colors, active agents and/oremulsifiers may also be added at this time. A softener such as glycerinmay also be added at this time, along with syrup and a portion of thebulking agent/sweetener. Further portions of the bulking agent/sweetenermay then be added to the mixer. A flavoring agent is typically addedwith the final portion of the bulking agent/sweetener. A high-intensitysweetener is preferably added after the final portion of bulking agentand flavor have been added.

The entire mixing procedure typically takes from five to fifteenminutes, but longer mixing times may sometimes be required. Thoseskilled in the art will recognize that many variations of the abovedescribed procedure may be followed. Including the one-step methoddescribed in US patent application 2004/0115305 hereby incorporated asreference.

Structure of the Chewing Gum

According to the invention, the form and shape of the nicotine chewinggum may be any suitable and user friendly structure. Accordingly, thegum centre or gum may be e.g. in a form selected from a pellet, acushion-shaped pellet, a stick, a tablet, a chunk, a pastille, a pill, aball and a sphere. Chewing gums are formed by extrusion, compression,rolling and may be centre filled with liquids and/or solids in any form.

Coating

In accordance with the invention, the chewing gum element may compriseabout 0.1 to about 75% by weight of an outer coating applied onto thechewing gum centre. Thus, suitable coating types include hard coatings,film coatings and soft coatings of any composition including thosecurrently used in coating of chewing gum, pharmaceutical products andconfectioneries and any combination thereof.

One presently preferred outer coating type is a hard coating, which termis used in the conventional meaning of that term including sugarcoatings and sugar-free (or sugarless) coatings and combinationsthereof. The object of hard coating is to obtain a sweet, crunchy layer,which is appreciated by the consumer and it may moreover protect the gumcentres for various reasons. In a typical process of providing thechewing gum centres with a protective sugar coating, the gum centres aresuccessively treated in suitable coating equipment with aqueoussolutions of crystallisable sugar such as sucrose or dextrose, which,depending on the stage of coating reached, may contain other functionalingredients, e.g. fillers, binding agents, colours, etc. In the presentcontext, the sugar coating may contain further functional or activecompounds including flavour compounds and/or pharmaceutically activecompounds.

In the production of chewing gum it may, however, be preferred toreplace the cariogenic sugar compounds in the coating by other,preferably crystallisable, sweetening compounds that do not have acariogenic effect. In the art such coating are generally referred to assugarless or sugar-free coatings. Presently preferred non-cariogenichard coating substances include polyols, e.g. sorbitol, maltitol,mannitol, xylitol, erythritol, lactitol, isomalt and tagatose which areobtained by industrial methods by hydrogenation of D-glucose, maltose,fructose or levulose, xylose, erythrose, lactose, isomaltulose andD-galactose, respectively and trehalose, which is a non-cariogene mono-di-saccharide.

In a typical hard coating process as it will be described in details inthe following, a suspension containing crystallisable sugar and/orpolyol is applied onto the gum centres and the water it contains isevaporated off by blowing with air. This cycle must be repeated severaltimes, typically 3 to 80 times, in order to reach the swelling required.The term “swelling” refers to the increase in weight or thickness of theproducts, as considered at the end of the coating operation bycomparison with the beginning, and in relation to the final weight orthickness of the coated products. In accordance with the presentinvention, the coating layer constitutes about 0.1 to about 75% byweight of the finished chewing gum element, such as about 10 to about60% by weight, including about 15 to about 50% by weight.

In further useful embodiments the outer coating of the chewing gumelement of the invention is an element that is subjected to a filmcoating process and which therefore comprises one or more film-formingpolymeric agents and optionally one or more auxiliary compounds, e.g.plasticizers, pigments and opacifiers. A film coating is a thinpolymer-based coating applied to a chewing gum centre of any of theabove forms. The thickness of such a coating is usually between 20 and100 μm.

Generally, the film coating is obtained by passing the chewing gumcentres through a spray zone with atomised droplets of the coatingmaterials in a suitable aqueous or organic solvent vehicle, after whichthe material adhering to the gum centres is dried before the nextportion of coating is received. This cycle is repeated until the coatingis complete.

In the present context, suitable film-coating polymers include ediblecellulose derivatives such as cellulose ethers including methylcellulose(MC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC) andhydroxypropyl methylcellulose (HPMC). Other useful film-coating agentsare acrylic polymers and copolymers, e.g. methylacrylate aminoestercopolymer or mixtures of cellulose derivatives and acrylic polymers. Aparticular group of film-coating polymers, also referred to asfunctional polymers are polymers that, in addition to its film-formingcharacteristics, confer a modified release performance with respect toactive components of the chewing gum formulation. Such release modifyingpolymers include methylacrylate ester copolymers, ethylcellulose (EC)and enteric polymers designed to resist the acidic stomach environment,yet dissolve readily in the duodenum. The latter group of polymersinclude: cellulose acetate phtalate (CAP), polyvinyl acetate phtalate(PVAP), shellac, metacrylic acid copolymers, cellulose acetatetrimellitate (CAT) and HPMC. It will be appreciated that the outer filmcoating according to the present invention may comprise any combinationof the above film-coating polymers.

In other embodiments, the film coating layer of the chewing gum elementsaccording to the invention comprises a plasticizing agent having thecapacity to alter the physical properties of a polymer to render it moreuseful in performing its function as a film-forming material. Ingeneral, the effect of plasticizers will be to make the polymer softerand more pliable as the plasticizer molecules interpose themselvesbetween the individual polymer strands thus breaking downpolymer-polymer interactions. Most plasticizers used in film coating areeither amorphous or have very little crystallinity. In the presentcontext, suitable plasticizers include polyols such as glycerol,propylene glycol, polyethylene glycol, e.g. the 200-6000 grades hereof,organic esters such as phtalate esters, dibutyl sebacate, citrate estersand thiacetin, oils/glycerides including castor oil, acetylatedmonoglycerides and fractionated coconut oil.

The choice of film-forming polymer(s) and plasticizing agent(s) for theouter coating of the present chewing gum element is made with dueconsideration for achieving the best possible barrier properties of thecoating in respect of dissolution and diffusion across the film ofmoisture and gasses.

The film coating of the chewing gum elements may also contain one ormore colourants or opacifiers. In addition to providing a desired colourhue, such agents may reflect light or form a barrier against moistureand gasses. Suitable colourants/pacifiers include organic dyes and theirlakes, inorganic colouring agents, e.g. titanium oxide and naturalcolours such as e.g. β-carotene or chlorophyll.

Additionally, film coatings may contain one or several auxiliarysubstances such as flavours and waxes or saccharide compounds such aspolydextrose, dextrins including maltodextrin, lactose, modified starch,a protein such as gelatine or zein, a vegetable gum and any combinationthereof.

In one specific embodiment the chewing gum centre is in the form of astick which is provided on at least one side with an edible filmcomprising layer of a coating of a film forming agent, e.g. a cellulosederivative, a modified starch, shallac, gum arabic, a dextrin, gelatine,zein, a vegetable gum, a synthetic polymer and any combination thereof,and a wax such as beeswax, carnauba wax, microcrystalline wax, paraffinwax and combinations thereof.

The following examples are given for illustration, but not limitation ofthe invention.

TABLE 1 Example 2 Example 3 Example 4 Ingredient Product I1 Product I2Product I3 Elastomers 6 12 3 Elastomer 30 20 15 plasticizers Waxes 8 8 4Softeners 6 6 3 Antioxidant 0.1 0.1 0.1 Calciumcarbonate 20 25 15 Bulksweetener 21 20 51 Nicotine 1.4 1.4 1.4 compound Buffer 3.0 3.0 3.0 HighIntensity 0.3 0.3 0.3 Sweetener Flavours 3.2 3.2 3.2 Glycerine 1 1 1Total 100.0 100.0 100.0

EXAMPLE 1 Preparation of Gum Base

Gum bases are prepared, which comprises the following ingredients:

Elastomers Elastomer plasticizers Waxes Softeners Fillers Anti oxidants

The detailed formulations are given in table 1. It should be emphasizedthat several other gum base compositions may be applied within the scopeof the invention.

The elastomers and fillers are added to the mixing kettle provided withmixing means like e.g. horizontally placed Z-shaped arms. The kettle hadbeen preheated for 15 minutes to a temperature of about 120 deg. C. Therubber is broken into small pieces and softened with mechanical actionin the kettle.

The elastomer plasticizer is slowly added to the elastomer until themixture becomes homogeneous. The remaining elastomer plasticizer is thenadded to the kettle and mixed for 10-20 minutes. The softeningingredients are added and mixed for 20-40 minutes until the wholemixture becomes homogeneous.

The mixture is then discharged into a pan and allowed to cool to roomtemperature from the discharge temperature of 120 deg. C.

EXAMPLE 2

Chewing gum is prepared by use of the gum base in example 1 formulatedaccording to table 1. A conventional mechanical mixing procedure is usedwith the use of only moderate heating.

Gum base and filler is mixed in a mixing kettle provided with mixingmeans like e.g. horizontally placed Z-shaped arms. The kettle had beenpreheated to a temperature of up to approximately 50 deg. C.

When the content is homogeneous the other ingredients are addedaccording to a specified time schedule. Nicotine is added in the firsthalf of the mixing process.

The pieces may be formulated with 0.1-8 mg of nicotine per piecepreferably 2-4 mg. The pieces evaluated comprise 2 mg nicotine perpiece.

The chewing gum was coated by means of hard coating. The coating maye.g. be applied according to the methods disclosed in the U.S. Pat. No.6,627,234, hereby included by reference.

EXAMPLE 3

Chewing gum is prepared by use of the gum base in example 1 formulatedaccording to table 1. A conventional mechanical mixing procedure is usedwith the use of only moderate heating.

Gum base and filler is mixed in a mixing kettle provided with mixingmeans like e.g. horizontally placed Z-shaped arms. The kettle had beenpreheated to a temperature of up to approximately 50 deg. C.

When the content is homogeneous the other ingredients are addedaccording to a specified time schedule. Nicotine is added in the firsthalf of the mixing process.

The pieces may be formulated with 0.1-8 mg of nicotine per piecepreferably 2-4 mg. The pieces evaluated comprise 2 mg nicotine perpiece.

The chewing gum was coated by means of hard coating. The coating maye.g. be applied according to the methods disclosed in the U.S. Pat. No.6,627,234, hereby included by reference.

EXAMPLE 4

Chewing gum is prepared by use of the gum base in example 1 formulatedaccording to table 1. A conventional mechanical mixing procedure is usedwith the use of only moderate heating.

Gum base and filler are mixed in a mixing kettle provided with mixingmeans like e.g. horizontally placed Z-shaped arms. The kettle had beenpreheated to a temperature of up to approximately 50 deg. C.

When the content is homogeneous the other ingredients are addedaccording to a specified time schedule. Nicotine is added in the firsthalf of the mixing process.

The pieces may be formulated with 0.1-8 mg of nicotine per piecepreferably 2-4 mg. The pieces evaluated comprise 2 mg nicotine perpiece.

The chewing gum was coated by means of hard coating. The coating maye.g. be applied according to the methods disclosed in the U.S. Pat. No.6,627,234, hereby included by reference.

EXAMPLE 5

The release of the active agent in Example 2-4 and two commercialproducts are determined in vitro. The test in vitro is carried out on achewing machine (European Pharmacopeia 4 th. ed. 2.9.25 Chewing gummedicated, drug release from) by chewing one piece of chewing gum atspecified time intervals 0, 1, 2, 3, 5, 7.5, 10, 20 and 30 minutes in aphosphate buffer with a pH of 7.4.

The results are illustrated and explained below

FIG. 1 illustrates a release profile of two prior art nicotine chewinggums as a function of time.

It is noted that the very initial and the intermediate release, isrelatively low over the period corresponding to a typical smoking timei.e. 5-8 minutes. The release rate from 0-1 minutes is even lower thanthe remaining intermediate release.

The two prior art nicotine chewing gums PA1 and PA2 are both intendedfor use by means of a chew process over approximately thirty minutes. Inother words, the intended build-up of nicotine in the blood of the useris a process running over quite a long while.

It is noted that both nicotine chewing gums appear to be releasingrelatively linear.

FIG. 2 illustrates the release of FIG. 1 in specific intervals of theabove-mentioned chewing gums PA1 and PA2 over the initial chewing periodof 0 to 5 minutes in intervals of 30 seconds. In other words a sort ofdifferential illustration of the release focusing on the release in theindividual sub-periods of the illustrated release time. As illustrated,the evaluated sub-periods are 0-½ minute, ½-1 minute, 1 minute-1½minute, 1½ minute-2 minute, 2 minute-2½ minute, 2½ minute-3 minute, 3minute-3½ minute, 3½-4 minutes, 4-4½ minutes and 4½-5 minutes.

It is noted that the very initial release and intermediate release, isincreasing relatively slow over a relatively long period compared to atypical smoking time in spite of the fact that the release showed inFIG. 1 appeared to be relatively constant.

FIG. 3 illustrates the initial and intermediate release of three chewinggums I1, I2 and I3 applicable according to the invention. The release,or transfer from the chewing gum to the exterior of the chewing gum, isillustrated in the same way as the prior art chewing gums of FIG. 2.

The illustrated chewing gums benefit of an initial advantageous releaseover the complete critical period of the first five to eight minutes ofsmoking. It is thus noted that the release is never below 2% per subperiod, i.e. 30 seconds. In other words, when the chewing gum is appliedaccording to the invention, a constant amount of nicotine may beavailable for transfer into the blood via the mucosa membrane.

It is also noted that the chewing I3 features a very significant releasein the first few minutes of the chewing process, thereby facilitating afast relief due to the fact that a high osmotic pressure on the mucosamembrane may be maintained from the very beginning.

It is further noted that the chewing gum I1 and I2 features a veryconstant release over the first 5 minutes of chewing. This may beregarded very advantageous when complying with e.g. the taste problemrelated to nicotine in the mouth.

FIG. 3 illustrates the resulting release obtained when a nicotinechewing gum is chewed in a chewing machine.

According to the invention, a nicotine chewing gum having the propertiesas illustrated in FIG. 3 may be applied according to the followingprocess steps.

A nicotine chewing gum, e.g. I1, I2 or I3 is provided to a user having ahuman body. The human user may then chew the chosen nicotine chewing gumand a fast relief with respect to craving may be obtained by thetransfer of nicotine from the nicotine chewing gum to the blood of theuser via the mucosa membrane.

As the applied nicotine chewing gum features a transfer of nicotine fromthe chewing gum above a chosen threshold transfer rate in the period ofabout ½ minute to about 2½ minutes from initiation of said chewingprocess a constant osmotic pressure may be maintained on the mucosamembrane during a relatively long intermediate period of the chewingprocess. In this way, a fast relief has been according to an embodimentof the invention.

It is noted that none of the chewing gums applied according to theinvention features a transfers of nicotine from the chewing gum below 2mg of nicotine per 30 second. It is also noted that e.g. 12 features amaintained dose of never below 4 mg per 30 second.

FIG. 4 illustrates the initial and intermediate release from the abovediscussed chewing gums PA1, PA2, I1, I2 and I3 over the initialapproximately 8 minutes of the chewing process. It is noted that thequickest releaser tends to flatten out after about 4-5 minutes ofchewing.

1. Method of relieving nicotine craving comprising the steps ofproviding at least one chewing gum comprising tobacco alkaloid to auser, providing relief of nicotine craving to said user by transferringof tobacco alkaloid from the chewing gum to the human body of said userby chewing of said chewing gum, said chewing of said chewing gumcomprising a chewing process involving a transfer of tobacco alkaloidfrom said chewing gum above a threshold transfer rate in the period ofabout ½ minute to about 2½ minutes from initiation of said chewingprocess.
 2. Method of relieving nicotine craving according to claim 1,wherein said tobacco alkaloid comprises nicotine.
 3. Method of relievingnicotine craving according to claim 1, wherein said transfer rate referto a transfer of nicotine from the chewing gum to the exterior of thechewing gum.
 4. Method of relieving nicotine craving according to claim1, wherein said threshold transfer rate is evaluated in sub periods ofthe period of about ½ minute to about 2½ minutes from initiation of saidchewing process.
 5. Method of relieving nicotine craving according toclaim 1, wherein said chewing of said chewing gum comprising a chewingprocess involving a transfer of tobacco alkaloid from said chewing gumabove a further threshold transfer rate in the period of about 2½minutes to about 10 minutes from initiation of said chewing processerably in the period of about.
 6. Method of relieving nicotine cravingaccording to claim 1, wherein said threshold transfer rate results in arelease of at least 2% of the tobacco alkaloid comprised in said chewinggum prior to chewing, every 30 seconds in the period from ½ minutes toabout 2½ minutes from initiation of said chewing process.
 7. Method ofrelieving nicotine craving according to claim 1, wherein said thresholdtransfer rate results in a release of at least 3% of the tobaccoalkaloid comprised in said chewing gum prior to chewing, every 30seconds in the period from about ½ minute to about 2½ minutes frominitiation of said chewing process.
 8. Method of relieving nicotinecraving according to claim 1, wherein said threshold transfer rateresults in a release of at least 5% of the tobacco alkaloid comprised insaid chewing gum prior to chewing, every 30 seconds in the period fromabout ½ minute to about 2½ minutes from initiation of said chewingprocess.
 9. Method of relieving nicotine craving according to claim 1,wherein said threshold transfer rate results in a release of at least 2%of the tobacco alkaloid comprised in said chewing gum prior to chewing,every 30 seconds in the period of about 2½ minutes to about 5 minutesfrom initiation of said chewing process.
 10. Method of relievingnicotine craving according to claim 1, wherein said threshold transferrate results in a release of at least 3% of the tobacco alkaloidcomprised in said chewing gum prior to chewing, every 30 seconds in theperiod of about 2½ minutes to about 5 minutes from initiation of saidchewing process.
 11. Method of relieving nicotine craving according toclaim 1, wherein said threshold transfer rate results in a release of atleast 4% of the tobacco alkaloid comprised in said chewing gum prior tochewing, every 30 seconds in the period of about 5 minutes to about 10minutes from initiation of said chewing process.
 12. Method of relievingnicotine craving according to claim 1, wherein said threshold transferrate results in a release of at least 2 to 10% of the tobacco alkaloidcomprised in said chewing gum prior to chewing in the period of about 0seconds to about 30 seconds from initiation of said chewing process. 13.Method of relieving nicotine craving according to claim 1, wherein saidthreshold transfer rate results in a release of less than 14% of thetobacco alkaloid comprised in said chewing gum prior to chewing in theperiod of about 0 seconds to about 2½ minutes from initiation of saidchewing process.
 14. Method of relieving nicotine craving according toclaim 1, wherein said threshold transfer rate results in a release of atmost 18% of the tobacco alkaloid comprised in said chewing gum prior tochewing in the period of about 10 to about 30 minutes from initiation ofsaid chewing process.
 15. Method of relieving nicotine craving accordingto claim 1, wherein said threshold transfer rate results in a release ofat least 0.03 mg of the tobacco alkaloid comprised in said chewing gumprior to chewing, every 30 seconds in the period from about ½ minute toabout 2½ minutes from initiation of said chewing process.
 16. Method ofrelieving nicotine craving according to claim 1, wherein said thresholdtransfer rate results in a release of at least 0.05 mg of the tobaccoalkaloid comprised in said chewing gum prior to chewing, every 30seconds in the period from about ½ minute to about 2½ minutes frominitiation of said chewing process.
 17. Method of relieving nicotinecraving according to claim 1, wherein said threshold transfer rateresults in a release of at least 0.08 mg of the tobacco alkaloidcomprised in said chewing gum prior to chewing, every 30 seconds in theperiod from about ½ minute to about 2½ minutes from initiation of saidchewing process.
 18. Method of relieving nicotine craving according toclaim 1, wherein said threshold transfer rate results in a release of atleast 0.03 mg of the tobacco alkaloid comprised in said chewing gumprior to chewing, every 30 seconds in the period of about 2½ to about 5minutes from initiation of said chewing process.
 19. Method of relievingnicotine craving according to claim 1, wherein said threshold transferrate results in a release of at least 0.05 mg of the tobacco alkaloidcomprised in said chewing gum prior to chewing, every 30 seconds in theperiod of about 2½ minutes to about 5 minutes from initiation of saidchewing process.
 20. Method of relieving nicotine craving according toclaim 1, wherein said threshold transfer rate results in a release of atleast 0.08 mg of the tobacco alkaloid comprised in said chewing gumprior to chewing, every 30 seconds in the period of about 2½ minutes toabout 5 minutes from initiation of said chewing process.
 21. Method ofrelieving nicotine craving according to claim 1, wherein at least 0.5 mgof tobacco alkaloid is released within the initial 10 minutes of thechewing process.
 22. Method of relieving nicotine craving according toclaim 1, wherein different parts of the chewing gum is targeted tobaccoalkaloid transfer at different times or in different periods of thechewing process.
 23. Method of relieving nicotine craving according toclaim 1, wherein said chewing gum comprises a coating and wherein saidcoating comprises tobacco alkaloid.
 24. Method of relieving nicotinecraving according to claim 1, wherein said chewing gum comprisessubstantially hydrophilic polymers.
 25. Method of relieving nicotinecraving according to claim 1, wherein the variation of transfer rate isminimized.
 26. Method of relieving nicotine craving according to claim1, wherein said tobacco alkaloid is comprised in an ion exchange resin.27. Method of relieving nicotine craving according to claim 1, whereinsaid tobacco alkaloid comprises salts of nicotine.
 28. Method ofrelieving nicotine craving according to claim 1, wherein said tobaccoalkaloid comprises nicotine in its free from.
 29. Method of relievingnicotine craving according to claim 1, wherein the tobacco alkaloid isbuffered.
 30. Method of relieving nicotine craving according to claim 1,wherein the chewing process is less than 30 minutes.
 31. Method ofrelieving nicotine craving according to claim 1, wherein the chewingprocess is matching the smoking time of a cigarette.
 32. Method ofrelieving nicotine craving according to claim 1, wherein said chewinggum comprises a polymer system in an amount of from about 2 to about 99%by weight, flavour in an amount of about 0.001 to about 30% by weightand sweeteners in an amount of about 2% to about 80% by weight. 33.Method of relieving nicotine craving according to claim 1, wherein saidchewing gum comprises fillers in an amount of from about 0 to about 60%by weight, flavour in an amount of about 0.001 to about 30% by weightand sweeteners in an amount of about 2 to about 80% by weight. 34.Method of relieving nicotine craving according to claim 1, wherein saidchewing gum comprises high intensity sweeteners in an amount of fromabout 0.001 to about 3% by weight and flavour in an amount of about0.001 to about 30% by weight.
 35. Method of relieving nicotine cravingaccording to claim 32, wherein said polymer system comprises elastomersin an amount of about 0.1 to about 40% by weight of the chewing gum. 36.Method of relieving nicotine craving according to claim 32, wherein saidpolymer system comprises elastomer plasticizers in an amount of about 2to about 60% by weight of the chewing gum.
 37. Method of relievingnicotine craving according to claim 32, wherein said polymer systemcomprises wax in an amount of about 0 to about 30% by weight of thechewing gum.
 38. Method of relieving nicotine craving according to claim32, wherein said polymer system comprises softeners in an amount ofabout 2 to about 30% by weight of the chewing gum.
 39. Method ofrelieving nicotine craving according to claim 32, wherein said polymersystem comprises fillers in an amount of about 0 to about 50% by weightof the chewing gum.
 40. Method of relieving nicotine craving accordingto claim 32, wherein said polymer system comprises antioxidants in anamount of about 0 to about 5% by weight of the chewing gum.
 41. Methodof relieving nicotine craving according to claim 1, wherein at least onepiece of said chewing gum is chewed at a time.
 42. Method of relievingnicotine craving according to claim 1, wherein at least two pieces ofsaid chewing gum are chewed at a time.
 43. Method of relieving nicotinecraving according to claim 1, wherein at least one piece of said chewinggum is chewed a day.
 44. Method of relieving nicotine craving accordingto claim 1, wherein at least one piece of said chewing gum is chewedwhen the person craves for nicotine.
 45. Method of relieving nicotinecraving according to claim 1, wherein at least one piece of said chewingis chewed when the person needs treatment including tobacco alkaloid ornicotine.